Thursday, January 24, 2008

huperzine A

"Jake, a chiropractor can fix eighty percent of back pain after six to eight months of regular treatment and eighty percent of back injuries heal themselves in six to eight months. You might as well take that thirty-five dollars, burn it, and rub the ashes on your back!”- Scott Millington (medical student, a few years ago)

I have spent a few days buried neck-deep in a stack of papers lurnin’bout Alzheimer’s disease. I can’t tell you why this has been the case but I can easily share a story with you which I hope you will appreciate - the story of huperzine A.

This story has a little bit to do with Chinese folk medicine. Many of us really, really want to believe that ‘alternative medicines’ work but those damned doctors and scientists keep telling us that if they worked there would be no need to call them ‘alternative’.

Here's the problem: sick people are not ‘ordinary customers’ they are ‘patients’. They are vulnerable - and they are paying for a complex biological activity that they do not clearly understand. The only purchase guarantee they usually have is the word of their 'doctor'. Cheating a sick person is different from cheating any other type of consumer – it is unusually cruel and pathetic. It is one of the lowest forms of evil. And yet it is done all around us – every day. Rarely do homeopaths agree to submit their miracle pills and herbs to simple, double-blind, placebo-controlled, myth-busting clinical trials. That is where magical herbs die and only drugs remain.

Dementia is scary – the progressive decline of cognitive function. It is the loss of memory, concentration, functional abilities – sanity. Contrary to age-old wisdom dementia is not a ‘normal’ part of aging. Not even close. Most of us will die quick witted with a mind full of vivid memories. About ten percent of us will get dementia assuming we live long enough to do so. Seventy percent of dementias are caused by Alzheimer’s disease, the rest by Parkinson’s, Huntington’s, Vascular dementia, Alcohol and a few others. None are caused by ‘nothing’.

Until a few decades ago we knew ‘nothing’ about the inner workings of Alzheimer’s disease. Basically neurons died and brains got smaller. That’s not rocket science. Also - brain tissue under a microscope showed visible ‘plaques’ and ‘filaments’ but that didn’t help much either. Today things are a little different. Scientists really know their diseases. Biologists love big words – huge, ridiculous words. Watch:

Neuropathologicaly, Alzheimer’s disease is characterized by the presence of extracellular neuritic plaques composed of β-amyloid peptide and intracellular neurofibrillary tangles composed of abnormally phosphorylated tau protein. Neurochemically, this is accompanied by a deficit in cholinergic neurotransmission, particularly in the basal forebrain.

Yeah – thanks. And did you say 'tau' protein? Why does that protein get such a 'small word'? We now know a lot about Alzheimer's disease and the genetic and biochemical mechanisms that cause it. We are learning more about them every day. But the sad reality is this: thousands of scientists with billions of dollars, millions of mice, many different mazes, and lots of big words have been highly mobilized and motivated for decades and yet the truth remains essentially the same - we still can’t do anything about the plaques and the filaments. There is no cure or method of prevention of Alzheimer’s.

But we are not completely empty handed. We have understanding - we have progress – and we have a few somewhat-useful drugs! Actually there are four drugs. And they are all ‘symptomatic’ which means they are helpless against the ‘plaques’ and the ‘filaments’ and can’t change the course of the disease but they can make what is left of your brain work better. The four pills are: tacrine, donepezil, rivastigmine, and galanthamine. They are all proven to help AD patients remember things and ‘think gooder’. These are, to my knowledge, the only ‘officially proven’ hope for a sick person. But there are some issues. Tacrine was first (approved in 1993) and it causes serious liver damage so your doctor would have to be demented himself to prescribe it to you today. The others are newer and better. They are easy on the liver and only cause moderate combinations of nausea, vomiting, diarrhea, constipation, headache, dizziness, and sleep disturbance.

Here’s how they work. Acetylcholine is a fancy name for a handy little neurotransmitter. Acetylcholinesterase is an enzyme that naturally degrades acetylcholine. These four drugs inhibit this enzyme leaving more acetylcholine for you to ‘think’ with. It’s fairly simple.

Actually it was fairly simple – until the biochemical supernerds started to dig a little deeper. I just spent a week buried in some heavy, heavy journals and I like what I leaned enough that I have decided to share.

It turns out that some ‘acetylcholinesterase inhibitors’ now appear to be doing some 'other good stuff' that the patient didn't pay for. Some bonus activity for your dollar – much like an unexpected free upgrade to the first-class cabin on an overnight flight. This blog is no place for the details but essentially the underlying processes of Alzheimer’s are complicated and interconnected and some of these drugs – somehow – help with the ‘plaques’ and maybe even the ‘fillaments’. These are the first examples of actual 'changes' in the course of the disease. The amount of supporting literature filling up journals in the past five years is insane (no pun intended). Last year alone had multiple massive reviews summarizing hundreds of recent studies about how ‘old drugs’ are doing ‘new things’ that we didn’t know about until now. It’s pretty cool to read (if you like big words). Seems there are a lot of mice finding a lot of cheese at the end of the maze all over the world these days. Alzheimer’s research is a pretty hot place to be right now. Anyway – the drugs don’t ‘cure’ Alzheimers but for the first time ever they can at least potentially ‘in principle’ cure it! So the race is on to find new – better - cholinesterase inhibitors that do 'extra stuff' and come closer to actually ‘curing’ this beast.

Now to the title compound – ‘huperzine A’. This is an anti-Alzheimer’s drug already approved in China and in American phase II clinical trials right now. It is definitely not a cure - but it is probably as good, if not better than current drugs. And it has an interesting history.

The compound comes from a Chinese herb called huperzia serrata – a ‘club moss’ (whatever the heck that means). The herb is an ancient Chinese folk medicine called “Qian Ceng Ta” that has been used for centuries to treat lots of stuff including swelling, fever, blood disorders and - you guessed it - various forms of insanity and dementia. For many years now, the herb has been officially sold as a diatery supplement with claims that it treats memory loss and mental impairment.

In 1986 huperzine A was isolated from the huperzia serrata, characterized, and shown by Chinese scientists to improve memory and learning in mice (or rats or guinea pigs or cats – I don’t know). This was soon confirmed by tests in the US and Switzerland – presumably because some people didn't trust Chinese mice. In 1989 some frustrated-overworked-underpaid graduate student of organic chemistry at the University of Pittsburg, Pennsylvania, synthesized huperzine A for the first time in his fume hood (or perhaps on his bench). This probably made his mean boss very happy and proud. After 1989 the ball was rolling. It rolled fast in China and a little slower in the rest of the world - but it rolled. There are now more than 500 academic publications detailing various syntheses of huperzine A, preparation of analogues, and biological testing on assays, cell cultures, mice, mokeys, and finally 'forgetful people'. The compound is becoming 'kind of a big deal'. There are now more than 80 international patents related to huperazine A – and 20 of them were filed last year. It was officially approved in 'pill form' in China a few years ago but, like I said, it has been taken in 'herb form' there for many years. US clinical trials are in the works. Some doctors in the US 'prescribe' it already because it is available on the shelves in their local ChinaTown. Worldwide marketing rights are owned by ‘Marco Hi-Tech Joint Venture’ which is a global trading and finance firm formed to import huperazine A from China.

Huperzine A is not a cure for Alzheimers – it is just a treatment. It is a cholinesterase inhibitor like the rest. It has lately been demonstrated by some researchers to also do some other ‘extra good stuff'. And it does have the same nausea, diarrhea, etc. side-effects as all of the other cholinesterase inhibitors – although it sounds like they are less severe than the others.

I'm trying to make an important point – when 'alternative medicine' does work it is no longer called that - it graduates from 'alternative' school and receives the title of drug! I told you this whole story because I believe it proves that the global (or 'first world' or 'western' or whatever) medical community is more than happy to accept ‘chinese folk medicine’ if it actually works. And it is easy to prove that something works. Pharmaceutical companies are not retarded – most ‘folk medicines’ have been tested and re-tested and they continue to be 'alternative'. I believe there are very few effective unproven medicines left and if you are buying any I hope they are not expensive because you are probably being cheated - unless you consider the 'placebo effect' to be effective - which is fair I suppose. But believing you are better or even 'feeling' better is not the same as 'being' better. It might be interesting and even humorous to observe what happens when a doctor gives a patient a 'sugar pill' instead of a 'cold medicine' but it is neither interesting nor funny to play that game with a cancer, or with high blood pressure. Nor obesity for that matter - everywhere I look I see shameless theaft form vulnerable fat people.

And just to be clear - this argument does not apply to 'medicine men' in poor countries where people have no available alternatives to herbal medicine. I also support anyone offering exercise or diet expertise to people who are not ill. Yoga and vegetables and not-smoking are obviously healthy. The 'cheaters' I refer to are homeopaths and other shameless liars who use tricks and gimmicks to sell magnetic bracelets, mysterious supplements, or magical diet pills to Canadians or Australians who are either too vulnerable or too gullible to say no. If that sounds harsh - good.

That being said - most rules have rare exceptions and huperzine A appears to have been an example of such a case. Right up until very recently it was indeed an 'effective alternative medicine'. We know that because it is now a drug. Or almost a drug (if you tend to wait for the FDA). I suppose that this 'exception' was great news for the the many forgetful old Chinese people that have taken huperzine for years.

And as you might have gathered based on the quote form Scotty - I have visited a few chiropractors in my day. Especially when the volleyball was in full swing. I do believe they helped me... well... maybe. That's a tough one to call - pain sucks - even a little bit relief might be worth thirty-five dollars to me. They do have a 'college' after all - and some of them even use 'ultrasound' and act like sensible physiotherapists. I personally draw the line at not-letting a chiropractor anywhere near my neck!